She is a 1982 graduate of Northfield Mount Hermon School, an elite preparatory school in New England, for which she currently serves as the chair of the Arts Advisory Council. She then attended Northwestern University before transferring to Brown University, where she studied acting with Jim Barnhill and John Emigh and served on the board of Production Workshop, the university's student theatre group.[3] During her senior year at Brown, she performed in one of her father's plays as Lady Ada Lovelace in a production of Childe Byron, a drama in which Ada's father, the poet Lord Byron, mends a taut, distant relationship with his daughter.[6] Linney graduated from Brown in 1986.[7] She went on to study acting at the Juilliard School as a member of Group 19 (1986–1990), which also included Jeanne Tripplehorn.[8] Linney later received an honorary Doctor of Fine Arts degree from Juilliard when she delivered the school's commencement address in 2009.[9]

In the late 1980s, Linney did a stint on ABC's General Hospital portraying the character Louise Knotts. She was a counselor at the community center where Tom Hardy, the son of Audrey and Steve Hardy, worked. Linney starred as Mary Ann Singleton in the television adaptations of Armistead Maupin's Tales of the City books (1993, 1998, and 2001). She won her first Emmy Award[12] in 2002 for "Outstanding Lead Actress in a Miniseries or a Movie" for Wild Iris. In 2004, she won her second Emmy as "Outstanding Guest Actress in a Comedy Series," for her recurring role as the final love interest of Frasier Crane in the television series Frasier.[3] In 2008, she won an Emmy in the category "Outstanding Lead Actress in a Miniseries or a Movie" for her portrayal of Abigail Adams, wife of the second president of the United States, in the HBO miniseries John Adams.[3] In October 1994, Linney guest-starred in an episode of Law & Order (episode "Blue Bamboo") as Martha Bowen. She played a blonde American singer who successfully claimed "battered woman syndrome" as a defense to the murder of a Japanese businessman. Linney returned to series television as actress and executive producer in Showtime's half-hour series about cancer, The Big C, which debuted in mid-2010. She starred as a suburban wife and mother who explores the emotional ups and downs of suffering cancer, and the changes it brings to her life and her sense of who she is.[13] She won a Golden Globe award for her performance in January 2011. Since 2009, Linney has served as host of the PBS television series Masterpiece Classic.

In June, 2016, Laura Linney was asked whether she would make another Tales series if she were asked, to which she answered yes and then revealed that talks were in progress about a new series of Tales of the City set in modern-day San Francisco. Armistead Maupin himself then revealed that meetings had already taken place and both Linney and Olympia Dukakis were attached.